CV Stimulants Flashcards
Epinephrine (E)
• Receptors
• Effects
• Uses
Epinephrine
Receptors:
• alpha1=alpha2; ß1=ß2
Effects:
• Binds BOTH beta and alpha to cause HTN and rapid HR (respectively)
Uses:
• Anaphylaxis
• Cadiac Arrest
• Hypotension
Norepinephrine (NE)
• Receptors
• Effects
• Uses
Norepinephrine
Receptors:
• alpha1 > alpha2 > ß1
Effects:
• binds alpha mainly so you only get HTN
Uses:
• Hypotension (DECREASES RENAL PERFUSION)
Dopamine (DA)
• Receptors
• Effects
• Uses
Dopamine
Receptors:
D1=D2 > ß > alpha
Effects:
• binds ß and alpha at HIGH CONC. causing Rapid HR and HTN (respectively)
Uses:
• Unstable Bradycardia, Heart Failure, Shock
• Chronotropic Effects predominate at high Dose
Dobutamine
• Receptors
• Effects
• Uses
Dobutamine
Receptors:
• ß1 > ß2, alpha
Effect:
• Binds ß and alpha to cause Rapid HR and HTN (respectively)
Uses:
• Heart Failure (inotropic > chronotropic)
• Stress Tests
Isoproterenol [Isuprel]
• Receptors
• Effects
• Uses
Isoproterenol
Receptors:
• ß1 = ß2
Effect:
• Binds ß to cause rapid HR
Uses:
• Electrophysiologic Evaluation of Tachyarrythmia
• Can worsen ischemia
Phenylephrine
• Receptors
• Effects
• Uses
Phenylephrine
Receptors:
• alpha1 > alpha 2
Effect:
• Binds alpha to cause HTN
Uses:
• Hypotension
Ephedrine [Pretz-D]
• Receptors
• Effects
• Uses
Ephedrine
Receptors:
• alpha 1 > alpha2 > ß1
Effect:
• INDIRECT activation of alpha and beta cause HTN and increased HR (respectively)
Uses: • Hypotension of anesthesia • Narcolepsy • Nasal Congestion • Asthma • Bronchospasm
What is the effect of stimulating Beta-1 receptors?
• where are these found?
Location: Primarily found in Cardiovascular System
Effect: Accelerate Heart Rate and Increase the force of contraction
Uses:
What is the effect of stimulating Beta-2 receptors?
• where are these found?
Location: Beta-2 found in Skeletal muscle (also they are found in CV system with Beta-1 receptors)
Effect: stimulation leads to muscle relaxation and increased perfusion
Uses:
What is the difference in Direct-acting and Indirect acting Sympathomimetic Drugs?
Direct:
• acts on the POST-Synaptic membrane to stimulate the receptor Directly
Indirect:
• Increase Availability of NE (norepinephrine) and E (epinephrine) by acting on the PRE-SYNAPIC neuron
Mixed:
• Direct activation on Post-synaptic and stimulation of Neurotransmitter release from PRE-synaptic neuron
In what ways can drugs indirectly act on neurons?
- Releasing or Displacing NE
- Blocking NE transport into sympathetic neurons
- Blocking metabolizing enzymes (Monamine oxidase, MAO) or catechol-O-methyltransferase (COMT)
What effect does reserpine on:
• Direct-acting drugs
• Indirectly-acting drugs
• Mixed-acting drugs
Direct-acting:
• NO response reduction
• May INCREASE (why?)
Indirectly-acting:
• ABOLISHED responses because there is no NE to stimulate the release of
Mixed:
• Effects will be blunted by reserpine
What does reserpine do?
• Reserpine depletes NE (norepinephrine) from sympathetic neurons
Dopamine is dose dependent, what are its effects at the following concetrations:
• Low
• Intermediate
• High
Low:
• D1/D2 receptors predominate
Intermediate:
• Beta receptor actions are seen (tachycardia)
High:
• Alpha receptor actions are seen HTN
What are the effects of epinephrine?
• are they dose dependent?
***Yes they are dose dependent
Low Dose:
• ß - receptors are predominatly activated
• Increased HR and Decreased Peripheral Resistance (via ß2) WIDEN the Pulse pressure (aka the window between systolic and diastolic)
High Dose:
• alpha - receptors are stimulated
Explain what happens to the following and why, when NE is injected into someone:
• Peripheral Resistance
• Heart Rate
• BP
Peripheral Resistance:
• Increased - NE acts mostly on alpha-1 receptors to cause vasocontriction
Heart Rate:
• Decreased - reduced by BARORECEPTOR response to increased resistance
Blood Pressure:
• Both Systolic and Diastolic are raised
Explain what happens to the following and why, when E is injected into someone:
• Peripheral Resistance
• Heart Rate
• BP
Peripheral Resistance:
• Decreased - E acts on Beta-2 receptors mostly at low dose cause vasodilation in skeletal muscle
Heart Rate:
• Increased - E acts on Beta-1 receptors stimulating an increased contraction
Blood Pressure:
• Widened HIGHer SYSTOLIC and LOWER Diastolic
Explain what happens to the following and why, when Isoproterenol is injected into someone:
• Peripheral Resistance
• Heart Rate
• BP
Peripheral Resistance:
• Decreased - E acts on Beta-2 receptors mostly at low dose cause vasodilation in skeletal muscle
Heart Rate:
• Increased - E acts on Beta-1 receptors stimulating an increased contraction
Blood Pressure:
• Widened HIGHer SYSTOLIC and LOWER Diastolic
T or F: Isoproterenol and epinephrine have essentially the same effect on BP.
False, while the effects are similar isoproterenol is much more potent and widens the Systolic/Diastolic window even more because it has NO ALPHA ACTIVITY
Epinephrine
• Routes of Administration
• Adverse Effects
• Uses
Routes of Administration:
• Inhaled, IV, or IM
Adverse Effects:
• Cerebral Hemorrhage
• Ventricular Arrhythmias
• Angina
Treats:
• Hypersensitivity Reactions
• Used at Vasocontrictor w/ Local Anesthetics
• Restores cardiac rhythm in cardiac arrest
Why is epinephrine not given orally or SC if you want systemic effects?
• It vasocontricts really hard so drug cannot travel far
Why is administration of epinephrine often contraindicated with beta blockers?
• what adverse effect might be more likely?
- Epinephrine works on both Alpha and Beta receptors
* Vasodilatory effects of beta action helps to prevent insanely high increases in BP caused by alpha action
Epinephrine
• Effect on Heart
• Potential Problems
Heart:
• Directly stimulates ß-1 receptors
Effect:
INCREASED CO (cardiac output)
• High HR (increased SA node depolarization)
• Increased Amplitude of Action Potential
• Increased Rate of Phase 0 depolarization
• Shortens AV node refractory period
Problems:
• Fibrillation (in company of other drugs)
• Pro-arrhythmogenic
How do the effect of NE and E on the SA node differ from that of ACh?
• Why?
NE and E:
• Stimulate increased rates of of SA nodal discharge
ACh:
• Decreased the rate of SA nodal discharge by acting through Muscarinic (M2) receptors
Epinephrine
• Effect on Vasculature
• Beta-1/2 effects (renal, skeletal mm, coronary)
• Alpha Effects (skin)
Overall Sympathetic Effects:
Beta-1 /Beta-2 effects:
- Beta-1: JGA stimulated => Renin Secretion => renal vascular resistance => Decreased Renal Bloodflow => Na+, K+, Cl- retained
- Beta-2: Increased Skeletal Muscle Perfusion, Increased Disastole => Increased Coronary Blood Flow
- Both: Increased cardiac output leads to increased Pulmonary Arterial and Venous pressures
Alpha Effects:
• Decreased Perfusion of the Skin
Why does epinephrine shorten systole?
- Shortened Systole increases the duration of diastole
* Heart is perfused during Diastole
What is the major difference between NE and E when it comes to the heart?
• why?
Norepinephrine:
• Does NOT increase cardiac output (CO)
• NO role in accelerating heart rate - NO BETA-2 action
Epinephrine
• DOES increase CO
• DOES accelerate HR - through BETA-2
What is the difference in NE and E with respect to effects on blood pressure?
• why?
• Norepinephrine has a stronger effect on blood pressure because there is no Beta-2 action that acts to dilate blood vessels in the periphery
Adverse effects of Norepinephrine.
Problems:
• Fibrillation (in company of other drugs)
• Pro-arrhythmogenic
• More problems with BP compared to people given E
How is norepinephrine Administered?
• Side effects of administration?
Administration:
• IV
Side Effects:
• Necrosis at infusion side
• Diminished Organ Blood Flow
What are the steps in Epinephrine sythesis starting with tyrosine?
Tyrosine => Dopa => Dopamine => Norepinephrine => Epinephrine
Dopamine
• Uses/MOA
• Administration
• Fallbacks?
Uses/MOA:
• Acts on D1 receptors in the kidney to INCREASE RENAL PERFUSION => urine output will tell you if its working
Administration:
•Given IV
Drawback:
•Can only be given for in patient use because it has a SHORT DURATION OF ACTION and must be given IV
Dopamine
•Dose Dependent Effects
LOW: D1 action
• RENAL - Increases Perfusion (inc. GFR)
MODERATE: D1 and ß1 action
• Increased Cardiac Output (Contractility»_space; HR)
• Increased NE release from Nerve Terminals b/c of Dopamine stimulation
HIGH: Alpha action mainly
• Increased peripheral Vascular Resistance
Dobutamine
• Receptors acted on
• Effect
• Use
Receptors:
• ß1-agonist and Alpha-1 agonsit/antagonist (-/+ enantiomers)
• NO ACTIVITY ON DOPAMINE RECEPTORS
Effect:
• Increased Cardiac Output; Increased stroke volume with minimal effect on heart rate
How does Dobutamine increase stroke volume without affecting heart rate?
- INCREASED myocardial Contractility
- DECREASED left ventricular filling pressures
- INCREASED urinary output
Dobutamine
• Administration
• Uses
Administration:
• IV infusion
• VERY short T1/2 (2min)
Uses:
• Heart Failure or Acute MI
• Post Cardiac Surgery
Isoproterenol:
• Receptors
• Effect
Receptors:
• ONLY ACTS on ß1/2 receptors
Effect:
• Increased Cardiac Output
• Decreased Diastolic BP
Isoproterenol:
• Uses
• Administration
• Side Effects
Uses:
• Stimulates HR in pts. with Bradycardia or Heart Block
• Used in pts. waiting for Pacemakers
Administration:
• Parenteral or by aerosol
Side Effects: •Palpitations • Tachycardia • Headache • Flushing
Phenylephrine
• Receptors
• Effect
Receptors
• Alpha agonist (no ß activity)
Effect:
• Increased BP by increasing Systemic Arterial Vasoconstriction
• Reflex Decrease in BP and CO
Phenylephrine
• Uses
• Administration
• Adverse effects
uses:
• Control Hypotension
Administration:
• SC, IV, IM
Adverse Effects: • Angina, Anxiety • Hallucinations • HTN • Insomnia
Ephedrine
• MOA
• Effects
• Elimination
MOA:
Mixed action
• Enhances NE release from sympathetic neurons
• Direct agonist of Alpha and Beta Receptors
Effects:
•Increased HR and CO
• Increased BP (due to alpha receptor stimulation in vesssels)
Elimination:
• Eliminated Unchanged in the Urine
Ephedrine
•Uses
• Adverse Effects
uses:
• Hypotension
•Hypotension of Analgesia
Adverse Effects:
• Increased Cardiac Workload => Angina
• Ventricular Dysfunction and Palpitations
• Fatal Arrhythmias
